The first study planned will utilize females known to be receptive with males who have had sexual exposure prior to the test mating. In this way we hope to overcome the methodologic problems of large numbers of females who are not receptive, and the impaired mating performance of the males treated with methadone. For the latter we will utilize lower doses which will not produce sedation or weight loss. Should this procedure result in a high neonatal mortality rate we would be in a firm position to evaluate other agents. A second goal is to evaluate whether propoxyphene, a commonly employed analgesic and a derivative of methadone, shares the deleterious effects which we have noted. This drug will be administered in the same schedule as in the methadone studies. We will continue and extend our endocrine studies with the intra-ventricular administration of extremely low doses of methadone and measurement of neuroendocrine events such as LH release and testosterone. Presuming that we can demonstrate an acute fall in LH and testosterone we will utilize stereospecific agents and inhibitors. Finally, we plan to initiate studies on the binding of methadone to spermatozoa and the seminal fluids at various times following the administration of radiolabelled methadone. BIBLIOGRAPHIC REFERENCE: Joffe, J.., Peterson, J.M., Smith, D.J., and Soyka, L.F.; Sub-lethal effects on offspring of male rats treated with methadone before mating. Res. Comm. Chem. Path. Pharmacol. 13: 611-621, 1976.